Hydrochloric Acid → 3-((1H-indol-3-yl)methyl)-5-chloro-2-oxo-1-propylindolin-3-yl benzoate

HRID 1523098Notes

Reaction equation

HRID 1523098 reaction equation
[C:1]([O:9][CH:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([Cl:19])[CH:17]=2)[N:12]([CH2:20][CH2:21][CH3:22])[C:11]1=[O:23])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C(O[CH2:43][C:44]1[C:52]2[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=2)[N:46](C(=O)C2C=CC=CC=2)[CH:45]=1)(=O)C1C=CC=CC=1.Cl>C(OCC)(=O)C>[C:1]([O:9][C:10]1([CH2:43][C:44]2[C:52]3[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=3)[NH:46][CH:45]=2)[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([Cl:19])[CH:17]=2)[N:12]([CH2:20][CH2:21][CH3:22])[C:11]1=[O:23])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3251421Potassium bis(trimethylsilyl)amideHCID 90411032HCID 90411032, compoundHCID 904179755-Chloro-2-oxo-1-propylindolin-3-yl benzoate

Product 1

HCID 863014383-((1H-indol-3-yl)methyl)-5-chloro-2-oxo-1-propylindolin-3-yl benzoateYield 43%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To an oven dried flask cooled under argon equipped with a stir bar was added 5-chloro-2-oxo-1-propylindolin-3-yl benzoate (0.08 grams, 0.24 mmol, 0.2 M in toluene). While stirring at 0° C. KHMDS (0.3 mL, 0.26 mmol, 0.87 M, purchased from Fisher Scientific) was added. After approximately fifteen minutes a solution of (1-benzoyl-1H-indol-3-yl)methyl benzoate (0.02 grams, 0.06 mmol, 0.3 M in anhydrous DMF (purchased from Fisher Scientific)) was added. The reaction continued to stir overnight. The next day the reaction was acidified with 0.1M HCl, diluted with ethyl acetate and the two layers were separated. The aqueous layer was salted out and washed twice more with ethyl acetate. The combined organic solution was dried with sodium sulfate, filtered and concentrated. Purification was done on a Teledyne ISCO with silica gel using a hexanes ethyl acetate gradient. This was followed by a subsequent reverse phase purification using Teledyne ISCO with a C18 column and a water with 0.1% formic acid, acetonitrile gradient. 43% yield. 1H-NMR δ 8.05 (bs, NH), 8.00 (d, 2H), 7.57 (t, 1H), 7.50 (d, 1H), 7.42 (t, 2H), 7.30 (d, 1H), 7.18 (m, 2H), 7.08 (m, 2H), 6.78 (d, 1H), 6.61 (d, 1H), 3.71 (d, 1H), 3.60 (m, 1H), 3.51 (d, 1H), 3.40 (m, 1H), 1.35 (m, 2H), 0.74 (t, 3H). Calculated mass for C27H23ClN2O3, 458.14. Observed 481.1 (M+Na).

Workup

  1. customTo an oven dried flask
  2. temperaturecooled under argon
  3. customequipped with a stir bar
  4. stirringto stir overnight
  5. customthe two layers were separated
  6. washwashed twice more with ethyl acetate
  7. dry with materialThe combined organic solution was dried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification
  11. customThis was followed by a subsequent reverse phase purification

Sources & evidence

ORD record
ord-13f7ff63cfec4cf88835243781cbf41b
Source dataset
uspto-grants-2015_07
Patent number
US09079853B2

Reaction notes

Loading…